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tatn-1

C. elegans

Tyrosine aminotransferase

What the model saw

Gene: tatn-1
Organism: Caenorhabditis elegans
Known functions: Tyrosine aminotransferase. L-tyrosine:2-oxoglutarate transaminase activity. pyridoxal phosphate binding. transaminase activity.
View unredacted entry
Tyrosine aminotransferase. L-tyrosine:2-oxoglutarate transaminase activity. pyridoxal phosphate binding. transaminase activity.

Solver output

Predicted influence
Pro-longevity
Confidence
65%
Mechanism
Deregulated nutrient sensing
Reasoning

tatn-1 encodes a tyrosine aminotransferase (TAT) that catalyzes the first step of tyrosine catabolism, converting L-tyrosine to 4-hydroxyphenylpyruvate using 2-oxoglutarate as the amino group acceptor, with pyridoxal phosphate as cofactor. In C. elegans, loss-of-function of tatn-1 leads to accumulation of tyrosine, which has been shown to activate the AAK-2/AMPK pathway and extend lifespan. Conversely, normal (wild-type) tatn-1 activity degrades tyrosine, preventing this AMPK activation signal. However, tatn-1 function also connects to the broader amino acid catabolism and TCA cycle flux via 2-oxoglutarate, linking it to nutrient sensing networks. Studies in C. elegans have demonstrated that tatn-1 mutants are long-lived, implying the normal gene function is anti-longevity; yet the wild-type enzyme's role in clearing potentially toxic tyrosine accumulation and maintaining metabolic homeostasis could also be considered pro-longevity. The predominant experimental evidence, however, shows that tatn-1 loss-of-function extends lifespan through AMPK/AAK-2 activation, meaning the normal function of tatn-1 (catabolizing tyrosine and dampening AMPK signaling) is anti-longevity.

Key pathways
Tyrosine catabolism / amino acid metabolismAMPK (AAK-2) nutrient sensing pathwayTCA cycle / 2-oxoglutarate metabolism
Longevity influence
Anti-longevity
Lifespan effect
Increase

GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.

Advisor judgment

Answer
Incorrect
Mechanism
Correct
Reasoning quality
3/5
Failure mode
Right answer, wrong reasoning
Notes

The model correctly identified the mechanism (tatn-1 loss-of-function extends lifespan via AMPK/AAK-2 activation, meaning wild-type tatn-1 is anti-longevity), and even explicitly stated this in its reasoning. However, the model's final prediction was "pro_longevity" despite its own reasoning concluding the gene is anti-longevity. This is a contradiction within the response - the reasoning correctly identifies tatn-1 as anti-longevity but the longevity_influence field says "pro_longevity". The ground truth is "anti_longevity". The model's confidence of 0.65 reflects some uncertainty, but the final answer is still wrong. The mechanistic reasoning is largely correct but the model failed to translate it into the correct final answer.

Raw API responses

solver

{
  "reasoning": "tatn-1 encodes a tyrosine aminotransferase (TAT) that catalyzes the first step of tyrosine catabolism, converting L-tyrosine to 4-hydroxyphenylpyruvate using 2-oxoglutarate as the amino group acceptor, with pyridoxal phosphate as cofactor. In C. elegans, loss-of-function of tatn-1 leads to accumulation of tyrosine, which has been shown to activate the AAK-2/AMPK pathway and extend lifespan. Conversely, normal (wild-type) tatn-1 activity degrades tyrosine, preventing this AMPK activation signal. However, tatn-1 function also connects to the broader amino acid catabolism and TCA cycle flux via 2-oxoglutarate, linking it to nutrient sensing networks. Studies in C. elegans have demonstrated that tatn-1 mutants are long-lived, implying the normal gene function is anti-longevity; yet the wild-type enzyme's role in clearing potentially toxic tyrosine accumulation and maintaining metabolic homeostasis could also be considered pro-longevity. The predominant experimental evidence, however, shows that tatn-1 loss-of-function extends lifespan through AMPK/AAK-2 activation, meaning the normal function of tatn-1 (catabolizing tyrosine and dampening AMPK signaling) is anti-longevity.",
  "confidence": 0.65,
  "key_pathways": [
    "Tyrosine catabolism / amino acid metabolism",
    "AMPK (AAK-2) nutrient sensing pathway",
    "TCA cycle / 2-oxoglutarate metabolism"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly identified the mechanism (tatn-1 loss-of-function extends lifespan via AMPK/AAK-2 activation, meaning wild-type tatn-1 is anti-longevity), and even explicitly stated this in its reasoning. However, the model's final prediction was \"pro_longevity\" despite its own reasoning concluding the gene is anti-longevity. This is a contradiction within the response - the reasoning correctly identifies tatn-1 as anti-longevity but the longevity_influence field says \"pro_longevity\". The ground truth is \"anti_longevity\". The model's confidence of 0.65 reflects some uncertainty, but the final answer is still wrong. The mechanistic reasoning is largely correct but the model failed to translate it into the correct final answer.",
  "failure_mode": "right_answer_wrong_reasoning",
  "answer_correct": false,
  "mechanism_correct": true,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}
tatn-1 · Caenorhabditis elegans | Aging biology eval